FB2024_03 , released June 25, 2024
Allele: Hsap\GFAPUAS.cWa
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General Information
Symbol
Hsap\GFAPUAS.cWa
Species
H. sapiens
Name
FlyBase ID
FBal0283569
Feature type
allele
Associated gene
Associated Insertion(s)
Carried in Construct
Key Links
Transgenic product class
Nature of the Allele
Transgenic product class
Progenitor genotype
Carried in construct
Cytology
Description

UAS regulatory sequences drive expression of wild-type Hsap\GFAP coding sequences.

Allele components
Component
Use(s)
Encoded product / tool
Mutations Mapped to the Genome
Curation Data
Type
Location
Additional Notes
References
Variant Molecular Consequences
Associated Sequence Data
DNA sequence
Protein sequence
 
Expression Data
Reporter Expression
Additional Information
Statement
Reference
 
Marker for
Reflects expression of
Reporter construct used in assay
Human Disease Associations
Disease Ontology (DO) Annotations
Models Based on Experimental Evidence ( 0 )
Disease
Evidence
References
Modifiers Based on Experimental Evidence ( 0 )
Disease
Interaction
References
Comments on Models/Modifiers Based on Experimental Evidence ( 0 )
 
Disease-implicated variant(s)
 
Phenotypic Data
Phenotypic Class
Phenotype Manifest In
Detailed Description
Statement
Reference

Over-expression of two copies (but not one) of Hsap\GFAPScer\UAS.cWa driven in glia by Scer\GAL4repo.PU leads to Rosenthal fiber-like inclusion formations in 20 day old flies.

Expression of Hsap\GFAPScer\UAS.cWa under the control of Scer\GAL4repo does not affect developmental rate or eclosion. Overall brain structure appears normal at 1 day of age, as assayed by haematoxylin and eosin. A TUNEL assay for apoptotic cells does not reveal dying cells at 1 day after eclosion. However, increasing numbers of TUNEL-positive cells are seen as the animals age, indicating some limited toxicity. The TUNEL-positive cells are widespread, with no obvious predilection for particular areas of the brain. In the lamina, there is a trend towards decreased numbers of glial cells with advancing age and a significant loss of neurons at 10 and 20 days of age, consistent with a non-autonomous effect.

Expression of Hsap\GFAPScer\UAS.cWa in glial under the control of Scer\GAL4repo promotes the loss of GluRIIB-expressing neurons which is particularly apparent by 20 days after eclosion.

Flies expressing Hsap\GFAPScer\UAS.cWa in glial under the control of Scer\GAL4repo exhibit a significantly increased frequency of seizures in response to mechanical stimulation.

Flies expressing Hsap\GFAPScer\UAS.cWa in glial under the control of Scer\GAL4repo display some abnormal protein aggregation (although less than in Hsap\GFAPR79H.Scer\UAS mutants), with numerous eosinophilic, elongated and beaded inclusions. The number of inclusions increases with age.

Flies expressing Hsap\GFAPScer\UAS.cWa in glial under the control of Scer\GAL4repo display an increase in autophagy induction with age, with a modest induction present at 1 day after eclosion and more substantial induction at 10 and 20 days of age.

External Data
Interactions
Show genetic interaction network for Enhancers & Suppressors
Phenotypic Class
Enhanced by
Statement
Reference
Suppressed by
Statement
Reference
Phenotype Manifest In
Enhanced by
Statement
Reference

Hsap\GFAPUAS.cWa, Scer\GAL4repo has lamina phenotype, enhanceable by Catn1/Cat[+]

Hsap\GFAPUAS.cWa, Scer\GAL4repo has adult brain phenotype, enhanceable by Catn1/Cat[+]

Hsap\GFAPUAS.cWa, Scer\GAL4repo has lamina phenotype, enhanceable by Sod1n1/Sod[+]

Hsap\GFAPUAS.cWa, Scer\GAL4repo has adult brain phenotype, enhanceable by Sod1n1/Sod[+]

Suppressed by
Statement
Reference
Additional Comments
Genetic Interactions
Statement
Reference
Xenogenetic Interactions
Statement
Reference

Overexpression of l(2)eflScer\UAS.cWa in flies expressing Hsap\GFAPScer\UAS.cWa under the control of Scer\GAL4repo results in a significant reduction in cell death. In addition, expression of l(2)eflScer\UAS.cWa also decreases the number of seizures. Protection from cellular toxicity is accompanied by a significant reduction in the number of inclusion bodies and in activation of autophagy.

Overexpression of Hsp26Scer\UAS.cWa in flies expressing Hsap\GFAPScer\UAS.cWa under the control of Scer\GAL4repo results in a significant reduction in cell death. In addition, expression of Hsp26Scer\UAS.cWa also decreases the number of seizures. Protection from cellular toxicity is accompanied by a significant reduction in the number of inclusion bodies.

Overexpression of Hsp27Scer\UAS.cWa in flies expressing Hsap\GFAPScer\UAS.cWa under the control of Scer\GAL4repo results in a significant reduction in cell death. In addition, expression of Hsp27Scer\UAS.cWa also decreases the number of seizures. Protection from cellular toxicity is accompanied by a significant reduction in the number of inclusion bodies.

Overexpression of CatScer\UAS.cAa in flies expressing Hsap\GFAPScer\UAS.cWa under the control of Scer\GAL4repo results in a significant reduction in cell death. In addition, expression of CatScer\UAS.cAa also decreases the number of seizures. Protection from cellular toxicity does not alter the number of inclusion bodies.

A Catn1 heterozygous background significantly enhances Hsap\GFAPScer\UAS.cWa toxicity and increases the frequency of mechanically-stimulated seizures in these flies. An increase in cellular toxicity does not alter the number of inclusion bodies but does increase autophagy induction.

A Sodn1 heterozygous background significantly enhances Hsap\GFAPScer\UAS.cWa toxicity and increases the frequency of mechanically-stimulated seizures in these flies. Protection from cellular toxicity does not alter the number of inclusion bodies. An increase in cellular toxicity does not alter the number of inclusion bodies but does increase autophagy induction.

Overexpression of Hsap\HSPA1AScer\UAS.cWa in flies expressing Hsap\GFAPScer\UAS.cWa under the control of Scer\GAL4repo results in a significant reduction in cell death. In addition, expression of Hsap\HSPA1AScer\UAS.cWa also decreases the number of seizures. Protection from cellular toxicity is accompanied by a significant reduction in the number of inclusion bodies and in activation of autophagy.

Overexpression of Hsap\SOD1Scer\UAS.cWb in flies expressing Hsap\GFAPScer\UAS.cWa under the control of Scer\GAL4repo results in a significant reduction in cell death. In addition, expression of Hsap\SOD1Scer\UAS.cWb also decreases the number of seizures. Protection from cellular toxicity does not alter the number of inclusion bodies.

Expression of Eaat1Scer\UAS.cRa significantly suppresses the Hsap\GFAP toxicity, but does not influence inclusion formation, Hsap\GFAP solubility or autophagy induction.

Complementation and Rescue Data
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Mutant
Wild-type
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Synonyms and Secondary IDs (2)
Reported As
Symbol Synonym
Hsap\GFAPScer\UAS.cWa
Hsap\GFAPUAS.cWa
Name Synonyms
Secondary FlyBase IDs
    References (2)